HUE033449T2 - Novel octahydrothienoquinoline derivative, pharmaceutical composition comprising derivative, and use of these - Google Patents

Novel octahydrothienoquinoline derivative, pharmaceutical composition comprising derivative, and use of these Download PDF

Info

Publication number: HUE033449T2
Authority: HU; Hungary
Prior art keywords: alkyl; group; reference example; nmr; alkyl group
Prior art date: 2011-03-14

Application number

HUE12758328A

Other languages

English (en)

Hungarian (hu)

Inventor

Toshihiro Nishimura

Hirotaka Teranishi

Masako Yoshida

Yasunori Ueno

Kiyoshi Kasai

Original Assignee

Kissei Pharmaceutical

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2011-03-14

Filing date

2012-03-12

Publication date

2017-11-28

2012-03-12 Application filed by Kissei Pharmaceutical filed Critical Kissei Pharmaceutical

2017-11-28 Publication of HUE033449T2 publication Critical patent/HUE033449T2/en

Links

239000003814 drug Substances 0.000 title description 8
125000000217 alkyl group Chemical group 0.000 claims description 373
150000001875 compounds Chemical class 0.000 claims description 211
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 109
125000003545 alkoxy group Chemical group 0.000 claims description 73
-1 2,2-dimethylphenyl Chemical group 0.000 claims description 70
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 69
125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 claims description 62
125000003710 aryl alkyl group Chemical group 0.000 claims description 54
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 53
150000003839 salts Chemical class 0.000 claims description 51
125000001424 substituent group Chemical group 0.000 claims description 43
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 37
125000005843 halogen group Chemical group 0.000 claims description 35
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 27
125000004432 carbon atom Chemical group C* 0.000 claims description 26
102000004980 Dopamine D2 Receptors Human genes 0.000 claims description 24
108090001111 Dopamine D2 Receptors Proteins 0.000 claims description 24
208000018737 Parkinson disease Diseases 0.000 claims description 17
229910052739 hydrogen Inorganic materials 0.000 claims description 17
239000008194 pharmaceutical composition Substances 0.000 claims description 16
125000004122 cyclic group Chemical group 0.000 claims description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
125000003277 amino group Chemical group 0.000 claims description 13
239000004202 carbamide Substances 0.000 claims description 13
125000000753 cycloalkyl group Chemical group 0.000 claims description 13
125000003118 aryl group Chemical group 0.000 claims description 12
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 11
WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 11
WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 11
208000005793 Restless legs syndrome Diseases 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
208000031424 hyperprolactinemia Diseases 0.000 claims description 8
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
229940035678 anti-parkinson drug Drugs 0.000 claims description 7
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 7
QXWYKJLNLSIPIN-JGVFFNPUSA-N droxidopa Chemical compound OC(=O)[C@@H](N)[C@H](O)C1=CC=C(O)C(O)=C1 QXWYKJLNLSIPIN-JGVFFNPUSA-N 0.000 claims description 6
229960001104 droxidopa Drugs 0.000 claims description 6
102000003823 Aromatic-L-amino-acid decarboxylases Human genes 0.000 claims description 5
108090000121 Aromatic-L-amino-acid decarboxylases Proteins 0.000 claims description 5
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
229910052799 carbon Inorganic materials 0.000 claims description 5
239000003954 decarboxylase inhibitor Substances 0.000 claims description 5
125000001072 heteroaryl group Chemical group 0.000 claims description 5
XBBDACCLCFWBSI-ZETCQYMHSA-N melevodopa Chemical compound COC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 XBBDACCLCFWBSI-ZETCQYMHSA-N 0.000 claims description 5
229960001794 melevodopa Drugs 0.000 claims description 5
229940121948 Muscarinic receptor antagonist Drugs 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 4
239000000812 cholinergic antagonist Substances 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
208000011580 syndromic disease Diseases 0.000 claims description 4
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
239000008177 pharmaceutical agent Substances 0.000 claims description 3
230000002265 prevention Effects 0.000 claims description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
239000011593 sulfur Substances 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims 11
150000002367 halogens Chemical class 0.000 claims 11
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims 4
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 3
150000002431 hydrogen Chemical class 0.000 claims 3
125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
239000003112 inhibitor Substances 0.000 claims 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
125000006828 (C2-C7) alkoxycarbonyl group Chemical group 0.000 claims 1
RKAMCQVGHFRILV-UHFFFAOYSA-N 1-chlorononane Chemical compound CCCCCCCCCCl RKAMCQVGHFRILV-UHFFFAOYSA-N 0.000 claims 1
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 1
102000010909 Monoamine Oxidase Human genes 0.000 claims 1
108010062431 Monoamine oxidase Proteins 0.000 claims 1
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 1
239000002465 adenosine A2a receptor agonist Substances 0.000 claims 1
150000001721 carbon Chemical group 0.000 claims 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
239000000825 pharmaceutical preparation Substances 0.000 claims 1
KBJXDTIYSSQJAI-UHFFFAOYSA-N propylcarbamic acid Chemical compound CCCNC(O)=O KBJXDTIYSSQJAI-UHFFFAOYSA-N 0.000 claims 1
229940044551 receptor antagonist Drugs 0.000 claims 1
239000002464 receptor antagonist Substances 0.000 claims 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
125000005309 thioalkoxy group Chemical group 0.000 claims 1
238000005160 1H NMR spectroscopy Methods 0.000 description 292
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 177
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 105
239000000203 mixture Substances 0.000 description 104
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 76
210000004027 cell Anatomy 0.000 description 66
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
238000006243 chemical reaction Methods 0.000 description 45
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
238000003756 stirring Methods 0.000 description 33
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 32
239000002904 solvent Substances 0.000 description 31
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 24
239000003480 eluent Substances 0.000 description 23
239000011541 reaction mixture Substances 0.000 description 23
238000010898 silica gel chromatography Methods 0.000 description 23
238000010828 elution Methods 0.000 description 22
102000006969 5-HT2B Serotonin Receptor Human genes 0.000 description 21
108010072584 5-HT2B Serotonin Receptor Proteins 0.000 description 21
241000282414 Homo sapiens Species 0.000 description 21
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
238000001816 cooling Methods 0.000 description 20
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101000931901 Homo sapiens D(2) dopamine receptor Proteins 0.000 description 18
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239000012442 inert solvent Substances 0.000 description 18
239000002609 medium Substances 0.000 description 18
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
239000007858 starting material Substances 0.000 description 16
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YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
230000035484 reaction time Effects 0.000 description 15
229940076279 serotonin Drugs 0.000 description 15
230000004936 stimulating effect Effects 0.000 description 15
125000004093 cyano group Chemical group *C#N 0.000 description 14
239000012046 mixed solvent Substances 0.000 description 14
150000001412 amines Chemical class 0.000 description 13
239000007788 liquid Substances 0.000 description 13
239000013612 plasmid Substances 0.000 description 13
229940044601 receptor agonist Drugs 0.000 description 13
239000000018 receptor agonist Substances 0.000 description 13
238000012360 testing method Methods 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 12
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 12
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 12
239000012044 organic layer Substances 0.000 description 11
239000007787 solid Substances 0.000 description 11
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
229940096895 Dopamine D2 receptor agonist Drugs 0.000 description 10
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
239000011575 calcium Substances 0.000 description 10
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239000003795 chemical substances by application Substances 0.000 description 10
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239000002288 dopamine 2 receptor stimulating agent Substances 0.000 description 10
230000000694 effects Effects 0.000 description 10
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OLJGTANQPOJPIV-MBOZVWFJSA-N (4ar,6r,8ar)-2-acetamido-3-cyano-n-[2-(dimethylamino)ethylcarbamoyl]-8-methyl-n-propyl-4a,5,6,7,8a,9-hexahydro-4h-thieno[3,2-g]quinoline-6-carboxamide Chemical compound C([C@H]1C[C@H](CN(C)[C@@H]1C1)C(=O)N(C(=O)NCCN(C)C)CCC)C2=C1SC(NC(C)=O)=C2C#N OLJGTANQPOJPIV-MBOZVWFJSA-N 0.000 description 9
PJYJWXOMQPHSKB-IIDMSEBBSA-N (4ar,6r,8ar)-2-amino-3-cyano-n-[2-(dimethylamino)ethylcarbamoyl]-8-methyl-n-propyl-4a,5,6,7,8a,9-hexahydro-4h-thieno[3,2-g]quinoline-6-carboxamide Chemical compound C([C@H]1C[C@H](CN(C)[C@@H]1C1)C(=O)N(C(=O)NCCN(C)C)CCC)C2=C1SC(N)=C2C#N PJYJWXOMQPHSKB-IIDMSEBBSA-N 0.000 description 9
UHSKFQJFRQCDBE-UHFFFAOYSA-N Ropinirole hydrochloride Natural products CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 UHSKFQJFRQCDBE-UHFFFAOYSA-N 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
229910000027 potassium carbonate Inorganic materials 0.000 description 9
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 8
239000002253 acid Substances 0.000 description 8
239000000939 antiparkinson agent Substances 0.000 description 8
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201000010099 disease Diseases 0.000 description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
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229910052757 nitrogen Inorganic materials 0.000 description 8
238000002360 preparation method Methods 0.000 description 8
125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 8
108091003079 Bovine Serum Albumin Proteins 0.000 description 7
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 7
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
150000001408 amides Chemical class 0.000 description 7
239000007864 aqueous solution Substances 0.000 description 7
239000013613 expression plasmid Substances 0.000 description 7
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125000004433 nitrogen atom Chemical group N* 0.000 description 7
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229960001879 ropinirole Drugs 0.000 description 7
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
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WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 6
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CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
108091028043 Nucleic acid sequence Proteins 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
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VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 5
JQMFQLVAJGZSQS-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)NC1=CC2=C(NC(O2)=O)C=C1 JQMFQLVAJGZSQS-UHFFFAOYSA-N 0.000 description 5
YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 5
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125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
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125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 description 1
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
125000005956 isoquinolyl group Chemical group 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
IQVRBWUUXZMOPW-PKNBQFBNSA-N istradefylline Chemical compound CN1C=2C(=O)N(CC)C(=O)N(CC)C=2N=C1\C=C\C1=CC=C(OC)C(OC)=C1 IQVRBWUUXZMOPW-PKNBQFBNSA-N 0.000 description 1
229950009028 istradefylline Drugs 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
230000002045 lasting effect Effects 0.000 description 1
108010009400 levodopa receptor Proteins 0.000 description 1
238000001638 lipofection Methods 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
230000005923 long-lasting effect Effects 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
229960000219 mazaticol Drugs 0.000 description 1
210000004245 medial forebrain bundle Anatomy 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
CEAJFNBWKBTRQE-UHFFFAOYSA-N methanamine;methanol Chemical compound NC.OC CEAJFNBWKBTRQE-UHFFFAOYSA-N 0.000 description 1
JDBJJCWRXSVHOQ-UTONKHPSSA-N methanesulfonic acid;(1r)-n-prop-2-ynyl-2,3-dihydro-1h-inden-1-amine Chemical compound CS(O)(=O)=O.C1=CC=C2[C@H](NCC#C)CCC2=C1 JDBJJCWRXSVHOQ-UTONKHPSSA-N 0.000 description 1
229940098953 methixene hydrochloride Drugs 0.000 description 1
RAOHHYUBMJLHNC-UHFFFAOYSA-N methixene hydrochloride Chemical compound [H+].O.[Cl-].C1N(C)CCCC1CC1C2=CC=CC=C2SC2=CC=CC=C21 RAOHHYUBMJLHNC-UHFFFAOYSA-N 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
ANGDWNBGPBMQHW-UHFFFAOYSA-N methyl cyanoacetate Chemical compound COC(=O)CC#N ANGDWNBGPBMQHW-UHFFFAOYSA-N 0.000 description 1
IYETZZCWLLUHIJ-UHFFFAOYSA-N methyl-(1-phenylpropan-2-yl)-prop-2-ynylazanium;chloride Chemical compound Cl.C#CCN(C)C(C)CC1=CC=CC=C1 IYETZZCWLLUHIJ-UHFFFAOYSA-N 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
230000007659 motor function Effects 0.000 description 1
125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
229960004927 neomycin Drugs 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
230000002474 noradrenergic effect Effects 0.000 description 1
239000002674 ointment Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
229960002275 pentobarbital sodium Drugs 0.000 description 1
125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
229960001511 pergolide mesylate Drugs 0.000 description 1
UWCVGPLTGZWHGS-ZORIOUSZSA-N pergolide mesylate Chemical compound CS(O)(=O)=O.C1=CC([C@H]2C[C@@H](CSC)CN([C@@H]2C2)CCC)=C3C2=CNC3=C1 UWCVGPLTGZWHGS-ZORIOUSZSA-N 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical class NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 1
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 description 1
125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
NKJQZSDCCLDOQH-UHFFFAOYSA-N piroheptine Chemical compound CC1N(CC)CCC1=C1C2=CC=CC=C2CCC2=CC=CC=C21 NKJQZSDCCLDOQH-UHFFFAOYSA-N 0.000 description 1
229950009232 piroheptine Drugs 0.000 description 1
239000004033 plastic Substances 0.000 description 1
230000001144 postural effect Effects 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 description 1
239000002243 precursor Substances 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
229960002262 profenamine Drugs 0.000 description 1
CDOZDBSBBXSXLB-UHFFFAOYSA-N profenamine Chemical compound C1=CC=C2N(CC(C)N(CC)CC)C3=CC=CC=C3SC2=C1 CDOZDBSBBXSXLB-UHFFFAOYSA-N 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
229960001956 rasagiline mesylate Drugs 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
229960003179 rotigotine Drugs 0.000 description 1
KFQYTPMOWPVWEJ-INIZCTEOSA-N rotigotine Chemical compound CCCN([C@@H]1CC2=CC=CC(O)=C2CC1)CCC1=CC=CS1 KFQYTPMOWPVWEJ-INIZCTEOSA-N 0.000 description 1
102220176144 rs759794906 Human genes 0.000 description 1
229950002652 safinamide Drugs 0.000 description 1
210000004761 scalp Anatomy 0.000 description 1
125000005920 sec-butoxy group Chemical group 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
229960003678 selegiline hydrochloride Drugs 0.000 description 1
229940026197 serotonin hydrochloride Drugs 0.000 description 1
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
239000006104 solid solution Substances 0.000 description 1
239000012453 solvate Substances 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
210000003523 substantia nigra Anatomy 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
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239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229960004558 terguride Drugs 0.000 description 1
125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
238000010257 thawing Methods 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
229960004479 trihexyphenidyl hydrochloride Drugs 0.000 description 1
QDWJJTJNXAKQKD-UHFFFAOYSA-N trihexyphenidyl hydrochloride Chemical compound Cl.C1CCCCC1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 QDWJJTJNXAKQKD-UHFFFAOYSA-N 0.000 description 1
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
WXAZIUYTQHYBFW-UHFFFAOYSA-N tris(4-methylphenyl)phosphane Chemical compound C1=CC(C)=CC=C1P(C=1C=CC(C)=CC=1)C1=CC=C(C)C=C1 WXAZIUYTQHYBFW-UHFFFAOYSA-N 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
238000003828 vacuum filtration Methods 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000011534 wash buffer Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
Epidemiology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Psychology (AREA)
Diabetes (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Endocrinology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

HUE12758328A 2011-03-14 2012-03-12 Novel octahydrothienoquinoline derivative, pharmaceutical composition comprising derivative, and use of these HUE033449T2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
JP2011055154		2011-03-14

Publications (1)

Publication Number	Publication Date
HUE033449T2 true HUE033449T2 (en)	2017-11-28

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ID=46830720

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Application Number	Title	Priority Date	Filing Date
HUE12758328A HUE033449T2 (en)	2011-03-14	2012-03-12	Novel octahydrothienoquinoline derivative, pharmaceutical composition comprising derivative, and use of these

Country Status (22)

Country	Link
US (1)	US9138434B2 (de)
EP (1)	EP2687532B1 (de)
JP (1)	JP5563716B2 (de)
KR (1)	KR101618624B1 (de)
CN (2)	CN103443106B (de)
AU (1)	AU2012227428B2 (de)
BR (1)	BR112013023575B1 (de)
CA (1)	CA2827629C (de)
DK (1)	DK2687532T3 (de)
ES (1)	ES2613658T3 (de)
HU (1)	HUE033449T2 (de)
IL (1)	IL228318A (de)
MX (1)	MX343077B (de)
MY (1)	MY183288A (de)
PH (1)	PH12013501856A1 (de)
PL (1)	PL2687532T3 (de)
PT (1)	PT2687532T (de)
RU (1)	RU2573399C2 (de)
SG (1)	SG193400A1 (de)
TW (1)	TWI537274B (de)
WO (1)	WO2012124649A1 (de)
ZA (1)	ZA201306905B (de)

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JP6166990B2 (ja) *	2012-09-12	2017-07-19	キッセイ薬品工業株式会社	オクタヒドロチエノキノリン誘導体の製造方法及びその製造中間体
US9585885B2 (en)	2012-12-10	2017-03-07	Kissei Pharmaceutical Co., Ltd.	Substituted pyrido[2,3-g]quinazolines as dopamine D2 receptor agonists
WO2014112492A1 (ja) *	2013-01-17	2014-07-24	キッセイ薬品工業株式会社	新規なオクタヒドロキノリン誘導体、それを含有する医薬組成物およびそれらの用途
KR102169337B1 (ko)	2018-08-22	2020-10-23	주식회사 도원엔바이로	질소와 인의 흡착형 세라믹 미생물 담체 및 이의 제조방법
DK4177257T3 (da)	2020-07-06	2026-03-02	Kissei Pharmaceutical	Succinat af octahydrothienoquinolinforbindelse, og krystaller deraf
CN116348470A (zh) *	2020-10-07	2023-06-27	橘生药品工业株式会社	八氢噻吩并喹啉化合物的制造方法和其制造中间体
TW202541802A (zh) *	2023-12-28	2025-11-01	日商橘生藥品工業股份有限公司	神經退化性疾病治療劑

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CH507249A (de)	1968-05-31	1971-05-15	Sandoz Ag	Verfahren zur Herstellung von 2-Brom-a-ergokryptin
BG17785A3 (bg)	1970-08-14	1973-12-25	Dr. Karl Thomae Gmbh	Метод за получаване на нови азетинови производни
US4166182A (en)	1978-02-08	1979-08-28	Eli Lilly And Company	6-n-propyl-8-methoxymethyl or methylmercaptomethylergolines and related compounds
PT69828A (en) *	1979-01-22	1979-07-01	Lilly Co Eli	Process for preparing octahydro-2h-pyrrolo-/3,4-g/quinolines
US4526892A (en) *	1981-03-03	1985-07-02	Farmitalia Carlo Erba, S.P.A.	Dimethylaminoalkyl-3-(ergoline-8'βcarbonyl)-ureas
US4452808A (en)	1982-12-07	1984-06-05	Smithkline Beckman Corporation	4-Aminoalkyl-2(3H)-indolones
US4501890A (en) *	1983-09-26	1985-02-26	Eli Lilly And Company	Trans-(±)-2,4,6-substituted-5,5a,6,7,8,9,9a,10-octahydro-pyrimido[4,5-g]quinolines
US4537893A (en) *	1984-04-27	1985-08-27	Eli Lilly And Company	Octahydrothiazolo[4,5-g]quinolines and use as prolactin secretion inhibitors
DE3572485D1 (en)	1984-12-22	1989-09-28	Thomae Gmbh Dr K	Tetrahydro-benzothiazoles, their production and their use as intermediates or drugs
US4826986A (en)	1986-06-16	1989-05-02	Eli Lilly And Company	6-Oxo-trans-octa- and decahydroquinolines
US5057515A (en) *	1989-07-24	1991-10-15	Eli Lilly And Company	Method for agonizing a dopamine receptor
US7026484B2 (en) *	2001-02-23	2006-04-11	Ligand Pharmaceuticals Incorporated	Tricyclic androgen receptor modulator compounds and methods
JP2005129430A (ja) *	2003-10-27	2005-05-19	Konica Minolta Holdings Inc	光電変換材料用半導体、光電変換素子及び太陽電池

2012
- 2012-03-09 TW TW101108043A patent/TWI537274B/zh active
- 2012-03-12 CA CA2827629A patent/CA2827629C/en active Active
- 2012-03-12 ES ES12758328.4T patent/ES2613658T3/es active Active
- 2012-03-12 CN CN201280013522.4A patent/CN103443106B/zh active Active
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- 2012-03-12 KR KR1020137026327A patent/KR101618624B1/ko active Active
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Also Published As

Publication number	Publication date
TWI537274B (zh)	2016-06-11
JPWO2012124649A1 (ja)	2014-07-24
AU2012227428B2 (en)	2016-05-05
ES2613658T3 (es)	2017-05-25
PL2687532T3 (pl)	2017-06-30
CN104829628A (zh)	2015-08-12
MX343077B (es)	2016-10-24
CA2827629A1 (en)	2012-09-20
NZ615293A (en)	2014-08-29
MX2013010587A (es)	2013-10-07
SG193400A1 (en)	2013-10-30
ZA201306905B (en)	2014-12-23
CN103443106A (zh)	2013-12-11
RU2013145799A (ru)	2015-04-20
IL228318A0 (en)	2013-11-25
KR20140010137A (ko)	2014-01-23
US9138434B2 (en)	2015-09-22
PH12013501856A1 (en)	2013-10-14
HK1188791A1 (zh)	2014-05-16
BR112013023575B1 (pt)	2021-12-21
KR101618624B1 (ko)	2016-05-09
EP2687532A1 (de)	2014-01-22
EP2687532B1 (de)	2016-12-14
WO2012124649A1 (ja)	2012-09-20
CA2827629C (en)	2019-01-08
CN103443106B (zh)	2015-09-30
US20140243311A1 (en)	2014-08-28
IL228318A (en)	2017-07-31
BR112013023575A8 (pt)	2018-01-16
BR112013023575A2 (pt)	2016-12-06
TW201242970A (en)	2012-11-01
MY183288A (en)	2021-02-18
AU2012227428A1 (en)	2013-09-26
CN104829628B (zh)	2018-01-09
JP5563716B2 (ja)	2014-07-30
DK2687532T3 (en)	2017-02-20
RU2573399C2 (ru)	2016-01-20
PT2687532T (pt)	2017-03-22
EP2687532A4 (de)	2014-08-13

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